The Role of the CuCl Active Complex in the Stereoselectivity of the Salt-Induced Peptide Formation Reaction: Insights from Density Functional Theory Calculations

Allison C Fox; Jason D Boettger; Eve L Berger; Aaron S Burton

doi:10.3390/life13091796

The Role of the CuCl Active Complex in the Stereoselectivity of the Salt-Induced Peptide Formation Reaction: Insights from Density Functional Theory Calculations

Life (Basel). 2023 Aug 23;13(9):1796. doi: 10.3390/life13091796.

Authors

Allison C Fox¹, Jason D Boettger², Eve L Berger³, Aaron S Burton³

Affiliations

¹ NASA Postdoctoral Program, NASA Johnson Space Center, Houston, TX 77058, USA.
² Department of Earth, Environmental and Resource Sciences, University of Texas at El Paso, El Paso, TX 79968, USA.
³ Astromaterials Research and Exploration Science Division, NASA Johnson Space Center, Houston, TX 77058, USA.

Abstract

The salt-induced peptide formation (SIPF) reaction is a prebiotically plausible mechanism for the spontaneous polymerization of amino acids into peptides on early Earth. Experimental investigations of the SIPF reaction have found that in certain conditions, the l enantiomer is more reactive than the d enantiomer, indicating its potential role in the rise of biohomochirality. Previous work hypothesized that the distortion of the CuCl active complex toward a tetrahedral-like structure increases the central chirality on the Cu ion, which amplifies the inherent parity-violating energy differences between l- and d-amino acid enantiomers, leading to stereoselectivity. Computational evaluations of this theory have been limited to the protonated-neutral l + l forms of the CuCl active complex. Here, density functional theory methods were used to compare the energies and geometries of the homochiral (l + l and d + d) and heterochiral (l + d) CuCl-amino acid complexes for both the positive-neutral and neutral-neutral forms for alanine, valine, and proline. Significant energy differences were not observed between different chiral active complexes (i.e., d + d, l + l vs. l + d), and the distortions of active complexes between stereoselective systems and non-selective systems were not consistent, indicating that the geometry of the active complex is not the primary driver of the observed stereoselectivity of the SIPF reaction.

Keywords: amino acid; biohomochirality; polymerization; salt-induced peptide formation; stereoselective.

Grants and funding

A.C.F.’s research was supported by an appointment to the NASA Postdoctoral Program at the NASA Johnson Space Center administered by Oak Ridge Associated Universities under contract with NASA. A.S.B. and E.L.B. were supported by NASA’s Planetary Science Division under the Internal Scientist Funding Model as well as the Goddard Center for Astrobiology. This material is also based upon research supported by the National Aeronautics and Space Administration through the NASA Astrobiology Institute under Cooperative Agreement no. 80NSSC18M0094 issued through the Science Mission Directorate.